The overarching aim of this application is to greatly expand knowledge about preclinical AD and specifically to characterize the chronology of biomarker changes, determine their path biological signatures (if any), and identify cognitively normal persons who are at very high risk for developing symptomatic AD. Successful treatment strategies will require biomarkers that can identify individuals at high risk for AD and at the earliest clinical stages in order to target them for clinical trials, disease- modifying therapies nd to monitor therapy success. The overall Specific Aims in this renewal application are to: 1. Follow the current participants in ACS and add new enrollees to maintain the sample size at ~300. 2. Obtain longitudinal data from the ACS participants at 2 year intervals with the following measures: a. Clinical and cognitive assessments (Clinical Core) b. Amyloid imaging with PET PIB (Project 1) c. Assays of amyloid-beta (A), tau, phosphorylated tau181 (p- tau181), and novel analytes in CSF and blood (Project 2, supported by the Biomarker Core) d. Attentional control battery and task-related functional MRI (fMRI) (Project 3) e. Structural MRI, resting state functional connectivity MRI (fcMRI), diffusion tensor imaging (DTI), and cerebral blood flow using arterial spin labeling (ASL) (Project 4) 3. Analyze associations among rates of change of all disease markers from all Cores and Projects (Data Management and Biostatistics Core).